Department of Bioengineering, Temple University, Philadelphia, Pennsylvania, United States of America.
National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2021 Feb 5;16(2):e0246298. doi: 10.1371/journal.pone.0246298. eCollection 2021.
One method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes. The inability to detect small effect sizes may be due to a neural compensatory mechanism known as "cross limb transfer", or the contribution of the contralateral limb to estimate an injured or perturbed limb's position. The robust transfer of compensation from the contralateral limb may obscure subtle locomotor outcomes that are evoked by clinically relevant therapies, in the early onset of disease, or between higher levels of recovery. Here, we propose angled rungs as a novel modification to the horizontal ladder walking task. Easily-adjustable angled rungs force rats to locomote across a different locomotion path for each hindlimb and may therefore make information from the contralateral limb less useful. Using hM3Dq (excitatory) Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in large diameter peripheral afferents of the hindlimb in the intact animal, we characterized the sensitivity of our design to detect stepping differences by comparing locomotor changes observed on angled rungs to those observed on a standard horizontal ladder. On our novel asymmetrical ladder, activation of DREADDs resulted in significant differences in rung misses (p = 0.000011) and weight-supporting events (p = 0.049). By comparison, on a standard ladder, we did not observe differences in these parameters (p = 0.86 and p = 0.98, respectively). Additionally, no locomotor differences were detected in baseline and inactivated DREADDs trials when we compared ladder types, suggesting that the angled rungs do not change animal gait behavior unless intervention or injury is introduced. Significant changes observed with angled rungs may demonstrate more sensitive probing of locomotor changes due to the decoupling of cross limb transfer.
一种用于评估感觉运动治疗干预的方法，即水平梯行走任务，分析疾病、损伤或外部操作后可能发生的运动变化。虽然这个任务非常适合检测大的影响，但它可能会忽略较小的变化。无法检测到小的效应大小可能是由于一种称为“交叉肢体转移”的神经补偿机制，或者对受伤或受干扰肢体位置的对侧肢体的贡献。来自对侧肢体的补偿的强大转移可能会掩盖由临床相关治疗、疾病早期发作或在较高恢复水平引起的微妙运动结果。在这里，我们提出了倾斜梯级作为水平梯行走任务的一种新的改进。可轻松调节的倾斜梯级迫使大鼠使用每条后腿穿过不同的运动路径，因此可能使来自对侧肢体的信息变得不那么有用。使用在完整动物的后肢大直径周围传入神经纤维中表达的 hM3Dq（兴奋性） Designer Receptors Exclusively Activated by Designer Drugs（DREADDs），我们通过将在倾斜梯级上观察到的运动变化与在标准水平梯级上观察到的运动变化进行比较，来描述我们的设计检测步幅差异的灵敏度。在我们的新型不对称梯级上，激活 DREADDs 导致梯级缺失（p = 0.000011）和承重事件（p = 0.049）的显著差异。相比之下，在标准梯级上，我们没有观察到这些参数的差异（p = 0.86 和 p = 0.98，分别）。此外，当我们比较梯级类型时，在基线和失活的 DREADDs 试验中都没有检测到运动差异，这表明除非引入干预或损伤，否则倾斜梯级不会改变动物的步态行为。在使用倾斜梯级时观察到的显著变化可能表明，由于交叉肢体转移的解耦，对运动变化的探测更加敏感。
